The affinity of blood for oxygen can be decreased acutely by the infusion of a solution of dihydroxyacetone, phosphate, and pyruvate or ortho-iodo sodium benzoate, using these methods, this proposed research will investigate the physiologic effect of a decrease in blood oxygen affinity on myocardial oxygen delivery, anaerobic metabolism, and blood flow distribution during pacing-induced ischemia in previously surgically prepared, conscious dogs (protocol 1). We will also determine whether the physiologic effects during pacing-induced ischemia can be maintained with a prolonged decrease in blood oxygen affinity (protocol 2), and whether the effects of a decrease in blood oxygen affinity and breathing 40% oxygen are additive (protocol 2). In addition, we will investigate if the anticipated metabolic benefits of a decrease in blood oxygen affinity provide a practical benefit by decreasing infarct size in rats subjected to acute coronary artery occlusion (protocol 4). Our goal is to establish whether increasing available oxygen by decreasing blood oxygen affinity is a useful and feasible form of therapy during myocardial ischemia.